PDLIM5
Chr 4PDZ and LIM domain 5
Also known as: ENH, ENH1, L9, LIM
This protein functions as a scaffold that tethers protein kinase C to the Z-disk region in cardiac muscle and regulates dendritic spine morphogenesis in neurons, playing roles in both heart development and synaptic growth regulation. Mutations cause autosomal recessive intellectual disability with seizures and cardiac abnormalities including cardiomyopathy. The gene is highly constrained against loss-of-function variants, suggesting complete loss of protein function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
154 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 16 | 0 | 16 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 78 | 7 | 0 | 85 |
Likely Benign | 0 | 4 | 3 | 2 | 9 |
Benign | 0 | 0 | 1 | 1 | 2 |
| Total | 0 | 82 | 31 | 3 | 116 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PDLIM5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools